Identification of molecular target of high risk pediatric AML by comprehensive genetic analysis
Project/Area Number |
16K20951
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Pediatrics
Hematology
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Research Institution | Yokohama City University (2017-2018) Gunma University (2016) |
Principal Investigator |
SHIBA NORIO 横浜市立大学, 医学部, 講師 (50600615)
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | 小児 / 急性骨髄性白血病 / DNAメチル化 / 抑制性ポリコーム / 遺伝子発現 / 治療層別化 / 予後予測 / メチル化アレイ / 遺伝子発現解析 / メチル化アレイ解析 / プロテオーム解析 / 遺伝子変異解析 |
Outline of Final Research Achievements |
Lots of gene alterations were identified and used for risk stratification by next generation sequencing. We investigated genome-wide DNA methylation patterns in pediatric patients with AML, and enabled to predict the prognosis particular in patients with FLT3-ITD which was known as adverse prognostic marker. Surprisingly, when we examined the relation between high PRDM16 expression and PRDM16 methylation sites, most of hypermethylatedion sites were gene body, and located at important regions which were the targets of repressed polycomb in leukemic blast cells.
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Academic Significance and Societal Importance of the Research Achievements |
小児、成人を問わず、急性骨髄性白血病は予後不良疾患であるが、今回の解析結果は、今後、不必要な造血幹細胞移植を回避したり、新たな分子標的薬の導入やメチル化阻害剤の適応症例の抽出などを可能とする可能性がある。その結果、治療成績の向上、移植治療関連死亡や治療関連の後遺症、合併症を減らすことができ、QOL向上に繋がることが期待される。
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Report
(4 results)
Research Products
(24 results)
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[Journal Article] Clinical and biological features of paediatric acute myeloid leukaemia (AML) with primary induction failure in the Japanese Paediatric Leukaemia/Lymphoma Study Group AML-05 study.2019
Author(s)
Miyamura T, Moritake H, Nakayama H, Tanaka S, Tomizawa D, Shiba N, Saito AM, Tawa A, Shimada A, Iwamoto S, Hayashi Y, Koike T, Horibe K, Manabe A, Mizutani S, Taga T, Adachi S.
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Journal Title
Br J Haematol.
Volume: 19
Issue: 2
Pages: 284-288
DOI
Related Report
Peer Reviewed
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[Journal Article] RUNX1 mutations in pediatric acute myeloid leukemia are associated with distinct genetic features and an inferior prognosis.2018
Author(s)
1.Yamato G, Shiba N, Yoshida K, Hara Y, Shiraishi Y, Ohki K, Okubo J, Park MJ, Sotomatsu M, Arakawa H, Kiyokawa N, Tomizawa D, Adachi S, Taga T, Horibe K, Miyano S, Ogawa S, Hayashi Y.
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Journal Title
Blood
Volume: Epub
Issue: 20
Pages: 2266-2270
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Risk-stratified therapy for children with FLT3-ITD-positive acute myeloid leukemia: results from the JPLSG AML-05 study.2018
Author(s)
Shimada A, Iijima-Yamashita Y, Tawa A, Tomizawa D, Yamada M, Norio S, Watanabe T, Taga T, Iwamoto S, Terui K, Moritake H, Kinoshita A, Takahashi H, Nakayama H, Koh K, Goto H, Kosaka Y, Saito AM, Kiyokawa N, Horibe K, Hara Y, Oki K, Hayashi Y, Tanaka S, Adachi S.
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Journal Title
Int J Hematol.
Volume: 107(5)
Issue: 5
Pages: 586-595
DOI
Related Report
Peer Reviewed
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[Journal Article] Prognostic impact of specific molecular profiles in pediatric acute megakaryoblastic leukemia in non-Down syndrome.2017
Author(s)
Hara Y, Shiba N, Ohki K, Tabuchi K, Yamato G, Park MJ, Tomizawa D, Kinoshita K, Shimada A, Arakawa H, Saito AM, Kiyokawa N, Tawa A, Horibe K, Taga T, Adachi S, Taki T, and Hayashi Y.
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Journal Title
Genes, Chromosomes & Cancer
Volume: 14 February 2017
Issue: 5
Pages: 394-404
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] ASXL2 Mutations are Frequently Found in Pediatric AML Patients with t(8;21)/RUNX1-RUNX1T1 and Associated with a Better Prognosis.2017
Author(s)
Yamato G, Shiba N, Yoshida K, Shiraishi Y, Hara Y, Ohki K, Okubo J, Okuno H, Chiba K, Tanaka H, Kinoshita A, Moritake H, Kiyokawa N, Tomizawa D, Park MJ, Sotomatsu M, Taga T, Adachi S, Tawa A, Horibe K, Arakawa H, Miyano S, Ogawa S, Hayashi Y.
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Journal Title
Genes Chromosomes Cancer.
Volume: -
Issue: 5
Pages: 382-393
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Outcome of relapsed core binding factor acute myeloid leukemia in children: A result from the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) AML-05R study.2017
Author(s)
Moritake H, Tanaka S, Nakayama H, Miyamura T, Iwamoto S, Shimada A, Terui K, Saito A, Shiba N, Hayashi Y, Tomizawa D, Taga T, Goto H, Hasegawa D, Horibe K, Mizutani S, Adachi S.
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Journal Title
Pediatr Blood Cancer
Volume: 64(10)
Issue: 10
DOI
Related Report
Peer Reviewed
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[Presentation] Clinical significance and prognostic analyses of PTPN11, RAS, and CBL mutations in pediatric AML -the JCCG study, JPLSG AML05-2018
Author(s)
Taeko Kaburagi, Genki Yamato, Norio Shiba, Yusuke Hara, Kentaro Ohki, Manabu Sotomatsu, Hirokazu Arakawa, Nobutaka Kiyokawa, Daisuke Tomizawa, Souichi Adachi, Takashi Taga, Keizo Horibe, Yasuhide Hayashi.
Organizer
日本血液学会
Related Report
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[Presentation] Prognosis of pediatric AML patient with FLT3-ITD is predicted by DNA methylation pattern; the JCCG study, JPLSG AML052018
Author(s)
Genki Yamato, Tomoko Kawai, Norio Shiba, Kentaro Ohki, Yusuke Hara, Nobutaka Kiyokawa, Daisuke Tomizawa, Akira Shimada, Manabu Sotomatsu, Hirokazu Arakawa, Souichi Adachi, Takashi Taga, Keizo Horibe, Kenichiro Hata, Yasuhide Hayashi.
Organizer
世界小児がん学会
Related Report
Int'l Joint Research
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[Presentation] 3.Comprehensive Analysis of 343 Genes using Targeted Sequencing Panel by Next-Generation Sequencer In 77 Pediatric AML Patients with Normal and Complex Karyotypes: JCCG Study, JPLSG AML-05.2018
Author(s)
Genki Yamato, Norio Shiba, Kenichi Yoshida, Yusuke Hara, Yuichi Shiraishi, Kentaro Ohki, Manabu Sotomatsu, Hirokazu Arakawa, Hidemasa Matsuo, Akira Shimada, Nobutaka Kiyokawa, Daisuke Tomizawa, Takashi Taga, Keizo Horibe, Satoru Miyano, Seishi Ogawa, Souichi Adachi, Yasuhide Hayashi
Organizer
米国血液学会
Related Report
Int'l Joint Research
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[Presentation] Transcriptome Analysis Revealed the Entire Genetic Understanding of Pediatric Acute Myeloid Leukemia with a Normal Karyotype2016
Author(s)
Shiba N, Yoshida K, Shiraishi Y, Hara Y, Yamato G, Kaburagi K, Sanada M, Ohki K, Park MJ, Tomizawa D, Chiba K, Tanaka H, Sotomatsu M, Arakawa H, Horibe K, Taga T, Adachi S, Tawa A, Miyano S, Ogawa S and Hayashi Y.
Organizer
58th Annual Meeting of the American Society of Hematology(ASH)
Place of Presentation
San Diego
Year and Date
2016-12-03
Related Report
Int'l Joint Research
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[Presentation] Identification of two distinct poor prognostic subgroups related to high expression of BMP2 or PRDM16 in pediatric AML2016
Author(s)
Hara Y, Yamato G, Shiba N, Okubo J, Ohki K, Park MJ, Sotomatsu M, Tomizawa D, Taki T, Kinoshita A, Kiyokawa N, Taga T, Arakawa H, Tawa A, Horibe K, Adachi S and Hayashi Y
Organizer
58th Annual Meeting of the American Society of Hematology(ASH)
Place of Presentation
San Diego
Year and Date
2016-12-03
Related Report
Int'l Joint Research
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[Presentation] Retrospective Evaluation of Correlations Between Genetic Backgrounds and Stem Cell Transplantation for De Novo Pediatric Acute Myeloid Leukemia2016
Author(s)
Kaburagi T, Yamato G, Shiba N, Hara Y, Ohki K, Ichikawa H, Park MJ, Shimada A, Sotomatsu M, Arakawa H, Horibe K, Adachi S, Taga T, Tawa A, Hayashi Y
Organizer
58th Annual Meeting of the American Society of Hematology(ASH)
Place of Presentation
San Diego
Year and Date
2016-12-03
Related Report
Int'l Joint Research
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